Methods and apparatus for non-invasively treating atrial fibrillation using high intensity focused ultrasound

ABSTRACT

Methods and apparatus are provided for non-invasively treating patent foramen ovale using an ultrasound imaging system and a high intensity focused ultrasound system to selectively target high intensity ultrasound energy on either or both of a patient&#39;s septum primum or septum secundum.

REFERENCE TO RELATED APPLICATIONS

This application claims priority from and is a Continuation-In-Part ofU.S. provisional patent application Ser. No. 60/477,532, filed Jun. 10,2003.

FIELD OF THE INVENTION

The present invention relates to methods and apparatus for treatment ofpatent foramen ovale, and more particularly, to the use of highintensity focused ultrasound non-invasively to treat patent foramenovale.

BACKGROUND OF THE INVENTION

Up until the 1980s, there was dramatic growth in the creation of newsurgical methods for treating a wide variety of previously untreatedconditions. Over the past twenty years there has been a clear trendtowards the invention of devices and methods that enable less-invasivetreatment of such diseases, moving from invasive surgery, and then toless-invasive surgery, and to interventional techniques. Ultimately, itis desirable to move to totally non-invasive therapies.

Patent foramen ovale (PFO) is characterized by a persistent fetalopening between the left and right atria of the heart that allows bloodto bypass the lungs. In most people, this opening permanently closesduring the first few months after birth. However, a PFO is present in upto 15 percent of adults.

PFO may be associated with various heart conditions includingparadoxical embolus, in which an embolus arising in venous circulationgains access to the arterial circulation through the PFO, therebyresulting in stroke or transient ischemic attack. Closure of PFO using atranscatheter approach may be medically necessary for patients with ahistory of cryptogenic stroke that are not candidates for anticoagulanttherapy. Implantable devices, such as those of AGA Medical Corporation(Golden Valley, Minn.) and NMT Medical, Inc. (Boston, Mass.) are used toclose PFOS.

It would be desirable to develop methods of treating PFO that are evenless invasive than transvascular interventional techniques, therebyeliminating the need for catheters.

The following devices pertain to the use of high intensity focusedultrasound (HIFU) energy to weld the tissues of a PFO closed. Eachdevice is used for application of energy to the tissues to be sealed.Heating of the tissues of the PFO by the HIFU causes a healing responsewhich causes the formerly separate tissues of the PFO to heal together.In some embodiments, the energy denatures the collagen of the tissues ofthe different portions of the PFO, and the tissues are caused to remainin close apposition in order to allow the collagen to bond while thetissue return to normal body temperature.

By way of example, WO 99/18871 and 99/18870 to Laufer, et al. (nowabandoned) describe the heating of the tissue of a PFO to induce closurethrough natural wound healing. These, however are invasive devices whichrequire entering and crossing the PFO. Additionally, U.S. Pat. No.6,562,037 to Paton et al. describes in detail methods and considerationsfor the rejoining of two tissue sections through the precise applicationof energy in a two-stage algorithm, wherein all voltage levels used areempirically derived and pre-programmed into the energy delivery controlsystem. Again, however, all devices described would need to be incontact with the tissues to be joined. Relevant articles from theclinical literature include “High-burst-strength, feedback-controlledbipolar vessel sealing”, Kennedy et al., Surg Endosc (1998) 12:876-878.This article describes the development of a system for use in open orlaparoscopic surgical procedures for achieving hemostasis inlarge-diameter arteries through the use of RF welding.

A wide variety of energy modes have been used to create lesions usingepicardial or intracardiac probes. Radio-frequency electrical energy,microwaves, cryothermia probes, alcohol injection, laser light, andultrasound energy are just a few of the technologies that have beenpursued.

Separately, several groups have developed focused ultrasound deviceswith both imaging and therapeutic capabilities. These efforts beganperhaps with lithotripsy, in which a high power focused ultrasoundsystem developed by Dornier Medizintechnik, Germany, was used to breakup kidney stones in the body. The kidney stones generally are locatedwithin the body at a significant depth from the skin. One ultrasoundimaging system is used to aim the system at the kidney stones, and thena second, high energy ultrasound system delivers energy that breaks upthe stones so they can be passed.

More recently, Therus Corp of Seattle, Wash., has developed a system toseal blood vessels after the vessels have been punctured to insertsheaths and catheters. The Therus system shrinks and seals femoralartery punctures at a depth of approximately 5 cm.

In addition, Timi-3 Systems, Inc., Santa Clara, Calif., has developedand is testing a trans-thoracic ultrasound energy delivery system toaccelerate the thrombolysis process for patients suffering an acutemyocardial infarction. This system delivers energy at a frequencyintended to accelerate thrombolysis without damaging the myocardium orvasculature of the heart.

Epicor Medical, Inc. of Sunnyvale, Calif., has developed a localizedhigh intensity focused ultrasound (“HIFU”) device to create lesions inthe atrial walls. The Epicor device is a hand-held intraoperativesurgical device, and is configured to be held directly against theepicardium or outside wall of the heart. When energized, the devicecreates full-thickness lesions through the atrial wall of the heart, andhas demonstrated that ultrasound energy may be safely and effectivelyused to create atrial lesions, despite presence of blood flow past theinterior wall of the atrium.

In addition, Transurgical, Inc., Setauket, N.Y. has been activelydeveloping HIFU devices. However, while the Epicor Medical devices areplaced in close approximation against the outside of the heart, theTransurgical devices are directed to intravascular catheters for heatingor ablating tissue in the heart and require that the catheter be broughtinto close approximation with the targeted tissue.

In view of the aforementioned limitations or previously-known devicesand methods, it would be desirable to provide methods and apparatus fortreating PFO by heating or ablating tissue at a distance from thattissue, so that the procedure may be performed non-invasively.

It also would be desirable to provide methods and apparatus for treatingPFO by applying energy from outside the body or from organs, such as theesophagus, that are easily accessible via natural body openings.

SUMMARY OF THE INVENTION

In view of the foregoing, it is an object of the present invention toprovide methods and apparatus for treating PFO so as to cause closure byablating or applying energy to weld the tissue at a distance from thattissue, so that the procedure may be performed non-invasively.

It is another object of the present invention to provide methods andapparatus for treating PFO by applying energy from outside the body orfrom neighboring organs, such as the esophagus, that are easilyaccessible.

These and other objects of the present invention are accomplished byproviding methods and apparatus that enable a physician to image tissuewithin the body that is to be heated or ablated, and then to heat orablate that tissue using a completely or relatively non-invasiveprocedure, and with little or no anesthesia. Advantageously, the methodsand apparatus of the present invention are expected to be cost-effectiveand time-efficient to perform compared to the previously-known surgicaland interventional procedures.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other objects and advantages of the present invention willbe apparent upon consideration of the following detailed description,taken in conjunction with the accompanying drawings, in which likereference characters refer to like parts throughout, and in which:

FIG. 1 is a schematic view of an illustrative imaging and treatmentultrasound system of the present invention;

FIG. 2 is a schematic view of an illustrative display of the imaging andtreatment ultrasound system of the present invention;

FIG. 3 is a schematic view showing the imaging and treatment ultrasoundsystem of FIG. 1 disposed adjacent to a cross-section of a patient'sthorax; and

FIG. 4 is a schematic view of the distal region of a catheter-based highintensity focused ultrasound array.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to methods and apparatus for creatinglesions in the walls of the heart or for ablating or welding the tissueof a PFO in a non-invasive manner using high intensity focusedultrasound (HIFU). Previously-known HIFU systems, such as those beingdeveloped by Epicor Medical or Transurgical, require close approximationof the HIFU device to the target tissue. These systems are not adaptedfor PFO closure. The methods and apparatus of the present inventionovercome this drawback by providing systems that enable the creation oflesions in the heart wall from a greater distance.

Referring to FIG. 1, apparatus constructed in accordance with theprinciples of the present invention is described. System 10 compriseshead 11 housing ultrasound imaging system 12 and high intensity focusedultrasound energy (“HIFU”) system 14. Ultrasound imaging system 12 andHIFU system 14 may have in common all or just a subset of thetransducers and related components, operating in different modes toimage or ablate. Head 11 is mounted on arm 13 that permits the head tobe positioned in contact with a patient (not shown) lying on table 15.Head 11 also may be a handheld unit, not needing an arm 13 to support orposition it. System 10 includes controller 16 that controls operation ofimaging system 12 and HIFU system 14. Monitor 18 displays images outputby imaging system 12 that allows the clinician to identify the desiredlocations on the walls of the heart to be treated.

In accordance with the methods of the present invention, controller 16and monitor 18 also are programmed to indicate the focus of the HIFUenergy relative to the image of the tissue cross-section. FIG. 2 showsillustrative screen display 19 of monitor 18 wherein the outline T ofthe tissue, as imaged by imaging system 12, and a marker correspondingto the location of focal point F of HIFU system 14, may be seen.

When activated, the HIFU system delivers ablative energy to the specificlocation shown on monitor 18 (focal point F in FIG. 2), thus enablingsafe creation of lesions or tissue welds. Because the HIFU system isconfigured to deliver energy from a number of sources focused towardsthe target tissue area, intervening tissue is subjected to only afraction of the energy deposited in the target tissue receives, and thusthe intervening tissue is not significantly heated or ablated.

Referring still to FIG. 1, ultrasound imaging system 12 may be similarin design to previously-known trans-thoracic ultrasound imaging systems,and are per se known. High intensity focused ultrasound system 14 maycomprise one or more HIFU generators 20 constructed as described in U.S.Patent Publication No. U.S. 20010031922A1. As mentioned before, imagingsystem 12 and HIFU system 14 also may use common elements. Preferably,each HIFU generator 20 is the same as or is disposed approximately inthe same plane as the imaging elements of ultrasound imaging system 12,so that the focus of HIFU system 14 occurs in the plane of the targettissue imaged by ultrasound imaging system 12. In addition, thisarrangement advantageously ensures that the HIFU energy will reach thetarget.

In a preferred embodiment, HIFU generators 20 deliver energy at afrequency optimized for heating myocardium, so that the lesions createdwill weld, occlude, or lead to the occlusion of the patent foramenovale. Once the lesions are created, a gradual healing process is begunin which the lesions fibrose, thus permanently sealing the opening.

While it may be possible to image and heat simultaneously, it may occurthat the output of HIFU system 14 may interfere with the ability toimage the tissue using ultrasound imaging system 12. Accordingly,controller 16 may be programmed to time-gate operation of imaging system12 and HIFU system 14, so that the tissue is alternately imaged andablated at a frequency of up to several times per second.

In order to apply energy to the wall of the septa of the heartsufficient to occlude the PFO, it may be desirable to slowly move thefocus of the HIFU system along the wall of the septa during the ablationprocess. While this may be accomplished by manually moving the HIFUsystem, it may alternatively be desirable to automate the process. Forexample, controller 16 may include suitable programming and joystick 22,or other input device, for refocusing the focal point of HIFU system 14along a desired trajectory.

Referring now to FIG. 3, according to an aspect of the presentinvention, an exemplary method of using the HIFU system to treat PFO isdescribed. More particularly, the HIFU system is used to createlocalized tissue heating of the septum primum and septum secundum thatwill lead to occlusion of a PFO. The consequent healing process isexpected to cause the septum primum and septum secundum to healtogether, thereby permanently closing the PFO or resulting in acutewelding of the tissues. Even if this non-invasive treatment were to beeffective in closing PFO in only a small percentage of cases, theprocedure would likely become the first choice for use in initialtherapy.

The tissues of the septum primum and the septum secundum preferably arein contact when the energy is applied to facilitate welding of the PFO.In cases where heat is applied to cause closure through scar formationand subsequent healing, it is also desirable to have the tissue inapposition to ensure that the correct target tissues are heated to anadequate degree to cause tissue damage. Adequate apposition exists inmany patients in the absence of an elevated right atrial pressure.However, in some cases it may be necessary or desirable to artificiallyincrease the pressure gradient between the right and left atria toensure closure of the PFO and/or to increase the contact pressurebetween the septum primum and septum secundum.

Closure of the PFO or increased contact pressure between the septumprimum and septum secundum can be achieved noninvasively through avariety of known techniques using medications, mechanical expedients, ora combination of the two. By way of example, briefly applying externalpressure to a patient's jugular veins will temporarily limit blood flowinto the superior vena cava and hence the right atrium. Of course, thislowers the right atrial pressure relative to the left atrial pressure,thereby creating the desired closure or increase in contact pressure.Alternatively, the desired closure or increase in contact pressure maybe achieved by administering drugs that increase the patient's bloodpressure by increasing heart rate and/or peripheral resistance. Onesuitable drug for increasing heart rate is epinephrine. As a furtheralternative, such drugs may be administered in combination with theapplication of pressure to the patient's jugular veins.

In the system shown in FIG. 3 the focus of the HIFU system is fixed at acertain point within the field of the ultrasound image. For example, theultrasound image might show a picture of rectangular planarcross-section of tissue with a fixed focus of the HIFU energy in thecenter of the field. In operation, the clinician manually moves theprobe until the desired tissue is in the target area, and then fires theHIFU system to ablate the tissue and occlude or weld the PFO. In orderto ablate tissue located less than 130 mm below the skin and stillretain a continuous fluid path from the probe to the target, the HIFUsystem includes fluid-filled balloon 24 that covers the face of theprobe.

Balloon 24 preferably is filled with water and enables the clinician toreposition the probe at a variable distance from the skin. Balloon 24also permits the clinician to position the probe at any desired angle totarget tissue not aligned directly under the focal point of HIFU system14. Alternatively, the patient could sit in a tub of water, so thepatient's chest and the probe were both underwater, again ensuring acontinuous fluid path.

As a further alternative, controller 16 may be programmed so that thedepth of the focal point of the HIFU system is depth-adjustable relativeto the imaged tissue. Advantageously, the depth of the targeted tissuethen could be adjusted relative to the imaged field, so a smallerfluid-filled balloon, or no balloon, is used to maintain fluid contactwhile adjusting the angle of the imaged section or make minor changes inthe depth of the targeted tissue. WIPO Patent Publication No.WO/0145550A2 to Therus describes several ways to adjust the depth of thefocused energy by changing the radius of curvature of one or more of theultrasound generators. Alternatively, the direction of several focusedenergy generators of relatively fixed focal length could be shiftedrelative to one another to move the focal point.

In accordance with the principles of the present invention, focusedenergy is applied from outside the patient's body. Because ultrasoundenergy does not travel coherently through non-fluid filled tissue, suchas the lungs, positioning of the ultrasound imaging system and HIFUsystem at certain angles may be more advantageous for treatment ofspecific areas of the heart.

Accordingly, it may be desirable to locate the imaging system and HIFUsystem on a movable arm or to position it by hand so as to permit otherexternal approaches, such as from below the diaphragm on the leftanterior side of the body, so the ultrasound has a coherent path throughthe diaphragm and apex and ventricles of the heart to the septa.Application of the probe also may be made along a patient's back.

While in the preferred embodiment described hereinabove energy isdelivered from outside the body, situations may arise where it isdifficult to deliver the energy to the PFO tissue. Referring now to FIG.4, and in accordance with another aspect of the present invention,methods and apparatus are provided for positioning a probe inside thebody and closer to the targeted tissue, but still not necessarilyadjacent to it. Intraluminal probe 30 is configured to deliver HIFUenergy to the heart from the esophagus, from the aorta, or from thegreat veins of the heart such as the inferior vena cava, superior venacava, or the right atrium itself.

This approach is fundamentally different from previously-known methodsof performing ablation during surgical procedures using epicardialprobes or during interventional procedures using intracardiac ablationcatheters. These previously-known devices are designed to be in directcontact or at least very close proximity (e.g., within 5 mm) of thetarget tissue, and are not designed to avoid ablation of interveningtissue between the probe and the target tissue.

Still referring to FIG. 4, catheter 30 preferably has a diameter in arange of 5 to 10 mm for vascular devices, and a diameter in a range of 5to 20 mm for an esophageal device. Imaging elements 32 and HIFU elements34 are arranged linearly along the longitudinal axis of the catheter.

The linear nature of the imaging element and HIFU element array mayimpose limitations on the ability to reposition the device. Whiletranslation and rotation of the catheter may be relatively easy, it iscontemplated that it may be difficult to move the device very far to oneside or another within a relatively small-diameter body lumen.

Accordingly, intraluminal catheter 30 preferably is configured to adjustthe focal point of the HIFU system with respect to both longitudinalposition and depth. This may be accomplished by programming thecontroller used with intraluminal catheter 30 to adjust the focal pointof the HIFU system, as described above. Alternatively, refocusing of thearray of HIFU elements may be achieved by locating individual HIFUelements on independently steerable actuators 36. Actuators 36 arecontrolled by the system controller and permit the clinician to move thefocal point of the HIFU array to any desired point in the field of viewof the imaging system.

In accordance with another aspect of the present invention, methods ofusing intraluminal catheter 30 to heat or ablate septal tissues from theesophagus to treat PFO are described. The esophagus is separated fromthe PFO by only about 20-25 mm, such that a lesion may be easily made inthe PFO using a probe capable of delivering energy at a distance ofapproximately 20-50 mm.

As described above, intraluminal catheter 30 preferably is configured,either mechanically or by suitable software algorithms, to move itsfocal point to enable a continuous linear ablation or heat affected zonewithout moving the device. Alternatively, the HIFU array of the cathetermay be configured to create a linear ablation or heat affected zone, orhave a fixed-focus so that a linear ablation or heat affected zone maybe created by translating the HIFU array within the esophagus.

In addition, it may be beneficial to cool tissue surrounding the HIFUarray of intraluminal catheter 30, to further reduce the risk of damageto the esophagus. Intraluminal catheter 30 may therefore include a waterjacket that circulates fluid around the HIFU array to prevent any heatgenerated by the array or ultrasound energy absorbed by the esophagusfrom causing any tissue damage.

Although preferred illustrative embodiments of the present invention aredescribed above, it will be evident to one skilled in the art thatvarious changes and modifications may be made without departing from theinvention. It is intended in the appended claims to cover all suchchanges and modifications that fall within the true spirit and scope ofthe invention.

1. Apparatus for non-invasively treating patent foramen ovalecomprising: a housing; an ultrasound imaging system disposed within thehousing; a high intensity focused ultrasound system disposed within thehousing in alignment with the ultrasound imaging system; and acontroller operably connected to the ultrasound imaging system and highintensity focused ultrasound system to selectively target high intensityultrasound energy on either or both of a patient's septum primum orseptum secundum.
 2. The apparatus of claim 1 wherein the controllerultrasound imaging system and the high intensity focused ultrasoundsystem comprise common transducers.
 3. The apparatus of claim 1 whereinthe controller is programmed to display a marker corresponding to afocal point of the high intensity focused ultrasound system.
 4. Theapparatus of claim 3 wherein the controller is programmed to adjust alocation of the focal point of the high intensity focused ultrasoundsystem within a two-dimensional plane orthogonal to an axis of the highintensity focused ultrasound system.
 5. The apparatus of claim 3 whereinthe controller is programmed to adjust a location of a depth of thefocal point of the high intensity focused ultrasound system.
 6. Theapparatus of claim 1 further comprising a fluid-filled balloon coupledto the housing to adjust a location of the focal point of the highintensity focused ultrasound system.
 7. The apparatus of claim 1 whereinthe patient's septum primum and septum secundum are apposed duringtreatment.
 8. The apparatus of claim 7, wherein apposition of thepatient's septum primum and septum secundum is achieved noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.
 9. Theapparatus of claim 7, wherein increased contact pressure between thepatient's septum primum and septum secundum is achieved noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.
 10. Amethod of non-invasively treating patent foramen ovale comprising:providing a housing having an ultrasound imaging system and a highintensity focused ultrasound system disposed in alignment with theultrasound imaging system; contacting the housing against a patient'sbody; operating the ultrasound imaging system to generate an image of aportion of cardiac tissue; and operating the high intensity focusedultrasound system, guided by the image, to heat or ablate either or bothof a patient's septum primum or septum secundum.
 11. The method of claim10 further comprising generating and displaying a marker correspondingto a focal point of the high intensity focused ultrasound system on theimage.
 12. The method of claim 10 further comprising modifying alocation of the target site by adjusting a location of the focal pointof the high intensity focused ultrasound system.
 13. The method of claim10 further comprising disposing a fluid-filled balloon between thepatient's body and the housing to adjust a location of the focal pointof the high intensity focused ultrasound system.
 14. The method of claim10 further comprising apposing the patient's septum primum and septumsecundum noninvasively using drugs, noninvasive procedures, or acombination thereof.
 15. The method of claim 10 further comprisingincreasing contact pressure between the patient's septum primum andseptum secundum is noninvasively using drugs, noninvasive procedures, ora combination thereof.
 16. Apparatus for intraluminally treating patentforamen ovale comprising: a catheter; an ultrasound imaging systemdisposed within the catheter; a high intensity focused ultrasound systemdisposed within the catheter in alignment with the ultrasound imagingsystem; and a controller operably connected to the ultrasound imagingsystem and high intensity focused ultrasound system to selectivelytarget high frequency ultrasound energy on either or both of a patient'sseptum primum or septum secundum.
 17. The apparatus of claim 16 whereinthe controller ultrasound imaging system and the high intensity focusedultrasound system comprise common components.
 18. The apparatus of claim16 wherein the controller is programmed to display a markercorresponding to a focal point of the high intensity focused ultrasoundsystem.
 19. The apparatus of claim 18 wherein the controller isprogrammed to adjust a location of the focal point of the high intensityfocused ultrasound system within a two-dimensional plane orthogonal toan axis of the high intensity focused ultrasound system.
 20. Theapparatus of claim 18 wherein the controller is programmed to adjust alocation of a depth of the focal point of the high intensity focusedultrasound system.
 21. The apparatus of claim 16 wherein the highintensity focused ultrasound system is configured to focus along alinear ablation target.
 22. The apparatus of claim 16 wherein thepatient's septum primum and septum secundum are apposed duringtreatment.
 23. The apparatus of claim 22, wherein apposition of thepatient's septum primum and septum secundum is achieved noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.
 24. Theapparatus of claim 22, wherein increased contact pressure between thepatient's septum primum and septum secundum is achieved noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.
 25. Amethod of treating patent foramen ovale comprising: providing a catheterhaving a distal portion housing an ultrasound imaging system and a highintensity focused ultrasound system disposed in alignment with theultrasound imaging system; disposing the distal portion of the catheterwithin a patient's body lumen; operating the ultrasound imaging systemto generate an image of a portion of cardiac tissue; and operating thehigh intensity focused ultrasound system, guided by the image, to heator ablate either or both of the patient's septum primum or septumsecundum.
 26. The method of claim 25, wherein the body lumen is theesophagus.
 27. The method of claim 25, wherein the body lumen is theaorta.
 28. The method of claim 25, wherein the body lumen is the rightatrium.
 29. The method of claim 25, wherein the body lumen is theinferior vena cava.
 30. The method of claim 25, wherein the body lumenis the superior vena cava.
 31. The method of claim 25 further comprisinggenerating and displaying a marker corresponding to a focal point of thehigh intensity focused ultrasound system on the image.
 32. The method ofclaim 25 further comprising modifying a location of the target site byadjusting a location of the focal point of the high intensity focusedultrasound system.
 33. The method of claim 25 further comprisingapposing the patient's septum primum and septum secundum noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.
 34. Themethod of claim 25 further comprising increasing contact pressurebetween the patient's septum primum and septum secundum is noninvasivelyusing drugs, noninvasive procedures, or a combination thereof.